Gilroy D W, Tomlinson A, Willoughby D A
Department of Experimental Pathology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
Inflamm Res. 1998 Feb;47(2):79-85. doi: 10.1007/s000110050285.
The anti-inflammatory effects of therapeutic dosing of drugs with greater selectivity for the inhibition of the constitutive (COX-1) or inducible isoform (COX-2) of cyclooxygenase were assessed in a model of chronic inflammation.
The murine chronic granulomatous tissue air pouch model involves the subcutaneous injection of air into the dorsum of mice followed 24 h later by the intrapouch injection of an inflammatory stimulus (0.5 ml of Freund's complete adjuvant containing 0.1% croton oil). Aspirin, more selective in vitro for the inhibition of COX-1 (10,200 (mg/kg) and nimesulide, a selective in vitro inhibitor of COX-2 (0.5, 5 mg/kg) were dosed p.o. daily from 3 days after injection of the inflammatory stimulus. Granuloma dry weight, vascularity and COX activity (measured as PGE2) were assessed at various time points throughout the inflammatory lesion to resolution at day 28. A second COX-2 inhibitor, NS 398 (0.1, 1, 10 mg/kg), was dosed p.o. daily from 3 days after the injection of the inflammatory stimulus and its effects on granuloma dry weight, vascularity and COX activity were measured at 7 days.
Aspirin (200 mg/kg) significantly inhibited levels of PGE2 throughout the time course and at the lower dose (10 mg/kg) from day 14. Nimesulide (5 mg/kg) however, significantly increased levels of PGE2 at days 5 and 21, but at 0.5 mg/kg was without effect. Aspirin (200 mg/kg) significantly reduced granuloma dry weight at day 14 but had no effect on granuloma vascularity at day 7. In contrast, nimesulide (5 mg/kg) significantly increased granuloma vascularity at day 7 and granuloma dry weight at day 14. NS-398 at all doses had no effect on granuloma dry weight, vascularity or COX activity 7 days after the injection of the inflammatory stimulus.
In this model of chronic inflammation, aspirin, more selective for the inhibition of COX-1 is more effective than the selective COX-2 inhibitors nimesulide and NS-398 at inhibiting granuloma dry weight, vascularity and COX activity.
在慢性炎症模型中评估了对环氧化酶组成型（COX - 1）或诱导型同工酶（COX - 2）具有更高选择性的药物治疗剂量的抗炎作用。
小鼠慢性肉芽肿组织气袋模型包括在小鼠背部皮下注射空气，24小时后在气袋内注射炎症刺激物（0.5毫升含0.1%巴豆油的弗氏完全佐剂）。阿司匹林在体外对COX - 1的抑制更具选择性（10、200毫克/千克），尼美舒利是一种COX - 2的体外选择性抑制剂（0.5、5毫克/千克），从注射炎症刺激物后第3天开始每日口服给药。在整个炎症病变至第28天消退的不同时间点评估肉芽肿干重、血管生成和COX活性（以PGE2测量）。第二种COX - 2抑制剂NS 398（0.1、1、10毫克/千克）从注射炎症刺激物后第3天开始每日口服给药，并在第7天测量其对肉芽肿干重、血管生成和COX活性的影响。
阿司匹林（200毫克/千克）在整个时间过程中显著抑制PGE2水平，在较低剂量（10毫克/千克）时从第14天开始起作用。然而，尼美舒利（5毫克/千克）在第5天和第21天显著增加PGE2水平，但在0.5毫克/千克时无作用。阿司匹林（200毫克/千克）在第14天显著降低肉芽肿干重，但在第7天对肉芽肿血管生成无影响。相比之下，尼美舒利（5毫克/千克）在第7天显著增加肉芽肿血管生成，在第14天增加肉芽肿干重。注射炎症刺激物7天后，所有剂量的NS - 398对肉芽肿干重、血管生成或COX活性均无影响。
在这个慢性炎症模型中，对COX - 1抑制更具选择性的阿司匹林在抑制肉芽肿干重、血管生成和COX活性方面比选择性COX - 2抑制剂尼美舒利和NS - 398更有效。
